Rafael Piñol

Joining Time-Resolved Thermometry and Magnetic-Induced Heating in a Single Nanoparticle Unveils Intriguing Thermal Properties

Whereas efficient and sensitive nanoheaters and nanothermometers are demanding tools in modern bio- and nanomedicine, joining both features in a single nanoparticle still remains a real challenge, despite the recent progress achieved, most of it within the last year. Here we demonstrate a successful realization of this challenge. The heating is magnetically induced, the temperature readout is optical, and the ratiometric thermometric probes are dual-emissive Eu(3+)/Tb(3+) lanthanide complexes. The low thermometer heat capacitance (0.021·K(-1)) and heater/thermometer resistance (1 K·W(-1)), the high temperature sensitivity (5.8%·K(-1) at 296 K) and uncertainty (0.5 K), the physiological working temperature range (295-315 K), the readout reproducibility (>99.5%), and the fast time response (0.250 s) make the heater/thermometer nanoplatform proposed here unique. Cells were incubated with the nanoparticles, and fluorescence microscopy permits the mapping of the intracellular local temperature using the pixel-by-pixel ratio of the Eu(3+)/Tb(3+) intensities. Time-resolved thermometry under an ac magnetic field evidences the failure of using macroscopic thermal parameters to describe heat diffusion at the nanoscale.

Structure–activity studies of ferroelectric and antiferroelectric imine ligands and their square-planar complexes

The synthesis and characterization of the mesomorphic and dielectric properties of a series of new imine-based liquid crystalline compounds that exhibit tilted SmC* phases is reported. The presence of an imino linkage within the mesogenic nucleus of these compounds is significant due to the ability of salicylaldimines to coordinate to metals. Structure–activity studies have also been carried out by varying the structural elements in the ligands. The structural variations include changing the length of the chiral chain and incorporating fluorocarbon segments in the achiral terminal chain.

Magnetic and relaxation properties of multifunctional polymer-based nanostructured bioferrofluids as MRI contrast agents

A series of maghemite/polymer composite ferrofluids with variable magnetic core size, which show a good efficiency as MRI contrast agents, are presented. These ferrofluids are biocompatible and can be proposed as possible platforms for multifunctional biomedical applications, as they contain anchoring groups for biofunctionalization, can incorporate fluorescent dyes, and have shown low cellular toxicity. The magnetic properties of the ferrofluids have been determined by means of magnetization and ac susceptibility measurements as a function of temperature and frequency. The NMR dispersion profiles show that the low frequency behavior of the longitudinal relaxivity r1 is well described by the heuristic model of 1H nuclear relaxation induced by superparamagnetic nanoparticles proposed by Roch and co‐workers. The contrast efficiency parameter, i.e., the nuclear transverse relaxivity r2, for samples with d > 10 nm assumes values comparable with or better than the ones of commercial samples, the best results obtained in particles with the biggest magnetic core, d = 15 nm. The contrast efficiency results are confirmed by in vitro MRI experiments at ν = 8.5 MHz, thus allowing us to propose a set of optimal microstructural parameters for multifunctional ferrofluids to be used in MRI medical diagnosis. Magn Reson Med, 2011.

Structure-activity studies of ferroelectric and antiferroelectric imine ligands and their palladium(II) complexes. An antiferroelectric metallomesogen

The synthesis and characterization of the mesomorphic and dielectric properties of new imine-based liquid crystalline compounds that exhibit tilted SmC* phases is reported. The presence of an imino linkage within the mesogenic nucleus of these compounds is significant due to the ability of benzaldimines to coordinate to metals. Complexation to a divalent metal such as Pd(II) has been studied in order to assess the effects of antiparallel dimerization of organic ligands, through metal-coordination, on the appearance of antiferroelectric order in the mesophase. An organometallic palladium(II) complex has been prepared and this shows antiferroelectric behaviour over the whole range of the tilted smectic mesophase. Structure–activity studies have also been carried out by varying structural elements in the composition of the ligands. The changes include the disposition of the linking groups within the mesogenic core, and presence of a lateral hydroxy group.

Stimuli-responsive poly(4-vinyl pyridine) hydrogel nanoparticles: Synthesis by nanoprecipitation and swelling behavior

Stimuli-responsive polymer nanospheres of poly(4-vinyl pyridine) have been obtained using a very simple modified nanoprecipitation technique. This process is conducted without help of crosslinking or monomer polymerization, methods used until now for this purpose. The influence of the surfactant concentration used in the preparation on particle size, the stability and the swelling kinetics of these hydrogels are studied. Furthermore, the nanospheres are shown to be pH and ionic strength responsive, undergoing swelling with equilibration times in the range of days. Dynamic light scattering and scanning electron microscopy were used to determine the structure, size, dispersion and morphology of these materials. Due to their response to stimuli, these nanoparticles are of potential interest for a number of biomedical applications such as drug delivery or biosensors.

Controlling structural and magnetic properties of IONPs by aqueous synthesis for improved hyperthermia

Iron oxide nanoparticles (IONPs) were synthesized by a novel aqueous synthesis route which combines co-precipitation (CP) and hydrothermal (HT) treatment, termed CP + HT, and compared with IONPs obtained by the standard CP method. Properties of both types of IONPs, including their morphology, diameters, composition, structure and crystallinity, as well as magnetic properties and toxicity were studied and correlated with the synthesis route. Their potential application as mediators for hyperthermia treatment has been evaluated by the specific absorption rate (SAR). Studies showed that IONPs obtained by a novel CP + HT route have a more controlled morphology, structure and crystallinity, leading to better magnetic properties and SAR as compared to IONPs synthesized by CP. Reported IONPs are also not toxic as shown by two assays in two cell lines. These results suggest that our IONPs are suitable for biomedical applications, especially as mediators for the hyperthermia treatment.

Tuning Properties of Iron Oxide Nanoparticles in Aqueous Synthesis without Ligands to Improve MRI Relaxivity and SAR

Aqueous synthesis without ligands of iron oxide nanoparticles (IONPs) with exceptional properties still remains an open issue, because of the challenge to control simultaneously numerous properties of the IONPs in these rigorous settings. To solve this, it is necessary to correlate the synthesis process with their properties, but this correlation is until now not well understood. Here, we study and correlate the structure, crystallinity, morphology, as well as magnetic, relaxometric and heating properties of IONPs obtained for different durations of the hydrothermal treatment that correspond to the different growth stages of IONPs upon initial co-precipitation in aqueous environment without ligands. We find that their properties were different for IONPs with comparable diameters. Specifically, by controlling the growth of IONPs from primary to secondary particles firstly by colloidal and then also by magnetic interactions, we control their crystallinity from monocrystalline to polycrystalline IONPs, respectively. Surface energy minimization in the aqueous environment along with low temperature treatment is used to favor nearly defect-free IONPs featuring superior properties, such as high saturation magnetization, magnetic volume, surface crystallinity, the transversal magnetic resonance imaging (MRI) relaxivity (up to r2 = 1189 mM−1·s−1 and r2/r1 = 195) and specific absorption rate, SAR (up to 1225.1 W·gFe−1).

Cell compatibility of a maghemite/polymer biomedical nanoplatform

We are reporting the cytocompatibility and cellular fate of an iron oxide/polymer nanoplatform (IONP) in its most basic formulation, using both mesenchymal (vascular smooth muscle cells, VSMC), and epithelial (opossum kidney, OK) cells. The cytotoxicity and cell internalization of the nanoplatform has been evaluated in relation to time of exposure and concentration of different components. A series of samples with different iron oxide nanoparticle, sizes, hydrodynamic sizes and iron/polymer ratio have been examined. In all cases cytotoxicity is low, and it is mostly determined by the internalization rate, being higher in VSMC than in OK cells. The mean lethal dose has a very narrow threshold, and necrosis is the only cell death type. IONP uptake shows little incidence on oxidative stress, and inflammasome activation is only observed with the smaller IONP at high concentration. The internalization rate in VSMC is determined by the polymer concentration exclusively. In OK cells, internalization rate seems to increase with decreasing hydrodynamic size. Internalization occurs through clathrin-dependent endocytosis, as it is prevented by potassium depletion and chlorpromazine. IONP are directed and accumulated in lysosomes. Under IONP overload, lysosomal dysfunction would cause cell death using concentrations that are hardly achieved in vivo.

Hematotoxicity of magnetite nanoparticles coated with polyethylene glycol: in vitro and in vivo studies

Hematotoxicity of magnetite nanoparticles coated with dimercaptosuccinic acid (DMSA) and polyethylene glycol (PEG) has been evaluated by determining their safety in vitro and in vivo in a rat model up to 30 days after administration of a single dose. The in vitro analysis consists of global plasma coagulation (PT, aPTT, and fibrinogen) and platelet aggregation tests while the hematotoxicity studies in vivo include a complete blood count and the possible genotoxic effect analysis in the bone marrow hematopoietic function. Prolonged aPTT values indicate a higher anticoagulant effect for NP-DMSA compared with PEG-coated nanoparticles as a consequence of the higher surface charge of the former. The in vivo tests showed that these bioferrofluids do not cause genotoxic effects, affect erythropoiesis or increase the number of immature erythrocytes in the bone marrow at the analyzed dose. However, nanoparticle administration showed a significant effect on the leukocyte counts in animals treated with DMSA coated nanoparticles 24 h after injection. This response is not observed in animals treated with PEG modified nanoparticles which justifies the use of this polymer in biomasking strategies.

Polymer-coated superparamagnetic iron oxide nanoparticles as T2 contrast agent for MRI and their uptake in liver

Aim: To study the efficiency of multifunctional polymer-based superparamagnetic iron oxide nanoparticles (bioferrofluids) as a T2 magnetic resonance contrast agent and their uptake and toxicity in liver. Materials & methods: Mice were intravenously injected with bioferrofluids and Endorem®. The magnetic resonance efficiency, uptake and in vivo toxicity were investigated by means of magnetic resonance imaging (MRI) and histological techniques. Results: Bioferrofluids are a good T2 contrast agent with a higher r2/r1 ratio than Endorem. Bioferrofluids have a shorter blood circulation time and persist in liver for longer time period compared with Endorem. Both bioferrofluids and Endorem do not generate any noticeable histological lesions in liver over a period of 60 days post-injection. Conclusion: Our bioferrofluids are powerful diagnostic tool without any observed toxicity over a period of 60 days post-injection.